The objectives of the proposed studies are two-fold. l) Marked prolongation or renal allograft survival across the strong AgB histocompatibility locus (Brown Norway to Lewis) in rats has been obtained Via recipient pre-treatment with doses of whole blood as small as 0.1 cc. Serologic studies indicate the mechanism of action is active enhancement. The micro test of Takasugi for studies of cellular immunity is well adapted for the demonstration of enhancing antibodies as described by the Hellstroms. Utilizing this system, and the micro droplet cytotoxicity assay of Terasaki, we will determine the ideal dose-response relationship in the rat for pre-treatment with whole blood (given intravenously and in millipore chambers) and its sub components over a range of pre-treatment schedules. This treatment will be combined with recipient heterologus rabbit antilymphocyte serum (RARLS), splenectomy, donor irradiation (to reduce graft passenger leukocytes), to demonstrate that permanent graft survival across strong histocompatibility barriers can be produced by active enhancement without reliance on chronic immunosuppressive drugs. 2) We have the capability to transplant viable functioning rat islet cells. We will attempt to demonstrate that these islet cells can be transplanted across histocompatibility barriers, using active enhancement or a short, intense course of RARLS, shown by us to be effective for renal transplants given two weeks before transplantation. While one source for islet cells will be pancreatic tissue treated in the manner described by Lacy, a strong effort will be made to develop a practical method of growing sufficient quantities of pancreatic islet cells for transplantation in tissue culture. We feel this is the only feasible source for islet cell transplants in humans and have considerable expertise in this field. Multiplication of fetal islet cells in tissue culture will be stimulated via the use of glyburide and serum from growth hormone tumor-bearing rats, plus standard islet culture techniques. Post-transplant function will be followed by assays of serum glucose and ketones, urine ketone and glucose assays, and an insulin immunoassay.